Antioxidant and Cholinesterase Inhibitory Activities of Ethyl Acetate Extract of Terminalia chebula: Cell-Free in Vitro and in Silico Studies
Open accessAbstract
BACKGROUND: fruit would be a potential source. OBJECTIVE: fruit which is widely practiced in the Ayurvedic medicines for memory enhancement. MATERIALS AND METHODS: fruit (TCEA) was subjected to phytochemical investigation of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities and cell-free antioxidant activity. TCEA was further subjected to gas chromatography-mass spectrum (GC-MS) analysis. The bioactive compounds were analyzed for molecular docking with AChE and BuChE proteins. RESULTS: cell-free antioxidant assays demonstrated that TCEA possesses excellent free radical scavenging activity, reducing power, and potent metal-chelating activity. Total polyphenolic content of TCEA was 596.75 ± 0.35 µg gallic acid equivalents/mg of extract, which correlates with the antioxidant activity of TCEA. Molecular docking of compounds expounded in GC-MS analysis for AChE and BuChE enzyme activities revealed that methyl N-(N-benzyloxycarbonyl-beta-l-aspartyl)-beta-d-glucosaminide as the most potent compound with good predicted activities. CONCLUSION: Overall, the results revealed that the bioactive molecule methyl N-(N-benzyloxycarbonyl-beta-l-aspartyl)-beta-d-glucosaminide present in TCEA is a potential depressant for the treatment of AD and related neurodegenerative disorders. SUMMARY: ; GC-MS: Gas chromatography-mass spectrum; ROS: Reactive oxygen species; RNS: Reactive nitrogen species; AChE: Acetylcholinesterase; BuChE: Butyrylcholinesterase; NFT: Neurofibrillary tangles; Aμ: μ-amyloid; NSAIDS: Nonsteroidal anti-inflammatory drugs; FDA: Food and Drug Administration; RT: Room temperature; HCl: Hydrochloric acid; ATCI: Acetylthiocholine iodide; BTCI: Butyrylthiocholine iodide; BHT: Butylated hydroxytoluene; DPPH: 2,2-diphenyl-1-picrylhydrazyl; TCA: Trichloroacetic acid; GAE: Gallic acid equivalent; NICT: National Institute of Information and Communications Technology; 3D: Three-dimensional; PDB: Protein data bank; OPLS: Optimized potentials for liquid simulations; XP: Extra precision; SD: Standard deviation; ANOVA: Analysis of variance; EDTA: Ethylenediaminetetraacetic acid.
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Increased BChE activity, especially in the hippocampus and temporal cortex, may exacerbate cognitive decline by promoting amyloid-beta aggregation and plaque formation.
“Additionally, increased BChE activity, especially in the hippocampus and temporal cortex, may exacerbate this cognitive decline by promoting amyloid-beta aggregation and plaque formation, which are key features of AD [94,95].”
From Cholinesterase Inhibitors from Plants and Their Potential in Alzheimer’s Treatment: Systematic Review (2025) · cites this paper as [94]
The Results and Discussion section says BuChE levels rise as Alzheimer’s disease progresses and links BuChE to plaque changes and neuronal degeneration. It does not locate increased BuChE activity in the hippocampus or temporal cortex; its hippocampus passage concerns AChE instead. The source therefore supports the general BuChE–plaque link, but not the claim’s anatomical specificity. (LLM, conf=0.88)
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“Additionally, increased BChE activity, especially in the hippocampus and temporal cortex, may exacerbate this cognitive decline by promoting amyloid-beta aggregation and plaque formation, which are key features of AD [94,95].”
- Authors
- Natarajan, S., Govindaraju, A., Rajmohamed, M., Palanisamy, P., & Abdulkader, A.
- Affiliations
- King Saud University (SA)
- Venue
- Pharmacognosy Magazine
- Publisher
- SAGE Publications
- Published
- 2017
- Volume
- 13
- Issue
- 51
- Pages
- 437
- ISSN
- 0973-1296 (ISSN-L)
- PMC
- PMC5669079
- OpenAlex
- W2762013552
- Cited by
- 20
- References
- 49
- Citations by year
- 2026: 2 · 2025: 3 · 2023: 5 · 2022: 3 · 2020: 4 · 2019: 1 · 2018: 2
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- Pharmacognosy Magazine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Health Sciences › Medicine › Complementary and alternative medicine › Phytochemicals and Medicinal Plants
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Terminalia chebula, acetylcholinesterase inhibition, butyrylcholinesterase inhibition, antioxidant activity, ethyl acetate extract, Alzheimer's disease, neurodegenerative diseases, polyphenols, free radical scavenging
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